Researchers from the Universitat Autònoma de Barcelona report they can cure diabetes in large animals with a single session of gene therapy. Writing in Diabetes, they said the dogs recovered their health and no longer show symptoms of the disease. In some cases, monitoring continued for over four years, with no recurrence of symptoms.

The therapy is minimally invasive and consists of a single session of various injections in the animal's rear legs using simple needles that are commonly used in cosmetic treatments. These injections introduce gene therapy vectors, with a dual objective: to express the insulin gene, on the one hand, and that of glucokinase, on the other. Glucokinase is an enzyme that regulates the uptake of glucose from the blood.

When both genes act simultaneously they function as a "glucose sensor", which automatically regulates the uptake of glucose from the blood, thus reducing diabetic hyperglycemia (the excess of blood sugar associated with the disease).

The research group had already tested this type of therapy on mice, but the new results with large animals may lay the foundation for the clinical translation of a gene therapy approach to veterinary medicine and eventually to diabetic patients.

The study data shows the safety of gene therapy mediated by adeno-associated vectors (AAV) in diabetic dogs. The therapy has proved to be safe and efficacious: it is based on the transfer of two genes to the muscle of adult animals using a new generation of very safe vectors known as adeno-associated vectors. These vectors, derived from non-pathogenic viruses, are widely used in gene therapy and have been successful in treating several diseases.

The first gene therapy medicine ever approved by the European Medicines Agency, Glybera®, makes use of adeno-associated vectors to treat a metabolic disease caused by a deficiency of lipoprotein lipase and the resulting accumulation of triglycerides in the blood.

Long-term control of the disease

Dogs treated with a single administration of gene therapy showed good glucose control at all times, both when fasting and when fed, improving on that of dogs given daily insulin injections, and with no episodes of hypoglycemia, even after exercise. Furthermore, the dogs treated with adeno-associated vectors improved their body weight and had not developed secondary complications four years after the treatment.

The study is the first to report optimal long-term control of diabetes in large animals. This had never before been achieved with any other innovative therapies for diabetes. The study is also the first to report that a single administration of genes to diabetic dogs is able to maintain normoglycemia over the long term (more than 4 years). As well as achieving normoglycemia, the dogs had normal levels of glycosylated proteins and developed no secondary complications of diabetes after more than 4 years with the disease.

There have been multiple clinical trials in which AAV vectors have been introduced into skeletal muscle, so the strategy reported in this study is feasible for clinical translation. Future safety and efficacy studies will provide the bases for initiating a clinical veterinary trial of diabetes treatment for companion animals, which will supply key information for eventual trials with humans. In conclusion, this study paves the way for the clinical translation of this approach to gene therapy to veterinary medicine, and eventually to diabetic patients.

Diabetes mellitus

Diabetes mellitus is the most common metabolic disease, and a large number of patients need insulin treatment to survive. In spite of the use of insulin injections to control the disease, these patients often develop serious secondary complications like blindness, kidney damage or amputation of limbs. Moreover, in order to achieve good blood glucose control, insulin has to be injected two or three times a day, which brings a risk of hypoglycemia episodes (lowering of blood sugar): an additional problem that comes on top of the other hardships of the treatment.

Comments

Thank you for sharing this info. It's very exciting. However, your explanation of diabetes is lacking and inaccurate in many ways. For an article on a "science" site, I expect more. For starters, clarify the difference between Type 1 and Type 2 Diabetes, and how ALL Type 1's need to use insulin. For us, it is not "to achieve good glucose control". It is to survive since our bodies do not make any insulin, unlike many Type 2s who make too much. Additionally, many of us Type 1s (that are not on the insulin pump) take 4-6 insulin shots a day. We must inject each time we eat (most people eat 3 times a day minimum) and 1-2 times for a slower acting (basal) insulin. And that doesn't factor in any correction shots for those times we miscalculate how many carbs are in what we eat, or sick days when our blood sugar rises without any food.

I appreciate the attempt to explain the "hardships" , but this feels disingenuous. Those of us who know, already know the WHOLE truth. Those who don't are usually reading to learn. Please help us teach accurate information. Thank you.

I'm not sure this therapy will help type 1s. Please examine what it's doing: Its regulating glucose uptake into cells and forcing the expression of the insulin gene. The problem with type 1 is, the immune system attacks the beta cells in the pancreas that make insulin and destroys them. This therapy doesn't halt the immune attack, so it follows (logically) that little insulin expression will be derived from it (in a type 1).

Now type II which is caused by an entire SEPARATE set of circumstances (low amounts of intact insulin production or insulin resistance) may logically benefit from this treatment because this treatment increases insulin production and increases bodily awareness of hyperglycemia (reducing insulin resistance).

IMO this is a therapy for type IIs, which is fine, but note it in the article please.

I have Type 1 diabetes. This disease is expensive to manage. I am covered by Romneycare in Massachusetts. Last year, just for the pharmacy items, I spent ~$700 for co-pays and insurance covered the rest, which was more like $7k. One doctors visit generates $1k worth of lab work, with four visits a year standard.

I have been able to maintain good control of my blood glucose levels with all this expensive efforts. That does represent a savings. People who cannot afford such aggressive management run higher glucose levels day to day. A major study showed that such people also have a higher incidence of all the complications that come with Type 1 diabetes: blindness, kidney failure, heart disease, amputations (second behind war vets), and sexual impotence. Those problems are often even bigger ticket items, so good glucose control - though expensive - can represent a savings overall, plus avoiding any of those conditions is a win for the patient.

I would be willing to buy my own plane ticket to Barcelona to get a one time shot in the leg to cure this threatening condition I have lived with for 29 years.

This is not at all an accurate depiction of the research published in the February edition of the Journal Diabetes that this author is referencing. Please don't publish things that are misleading to the millions of people dealing with Type ! diabetes. It is TERRIBLE science to give Type !'s a false hope that a few shots can cure their condition. You should be ashamed!

I had bad luck with Google, but the abstract is on line, not the full article. To quote their last line:

This study provides the first proof-of-concept in a large animal model for a gene transfer approach to treat diabetes.

From my reading, I think the article here was an accurate representation of that article which passed peer-review. As a diabetic for almost 3 decades, I am used to "proof-of-concept" ideas not working out. One of my favorites was the idea of taking islets from a pig and letting them live in a bio-safe plastic placed just under the skin. The human would provide the blood needed for the islet cells, the islets would do their normal thing. I recall thinking that approach had a great chance to work, it made so much sense. I am not sure what happened to this approach other than it has not reached patients.

If the news staff is referencing a specific technical article, I would appreciate it if there was a working link. I spent about 10 minutes trying to find the article in the Journal Diabetes, but to no avail. I would like to read the original, but it is hard without any of the researchers names. Particularly in light of MD's comments, I would like to investigate the issue myself. Any help would be appreciated (private communication is OK).

Again, it is a press release. We don't go out of our way to link to paywalled articles because they won't let anyone read them anyway, so it isn't very "Science 2.0" to endorse billion-dollar Science 1.0 corporations (or however much the ADA gets per year yet they still need to charge a subscription) using taxpayer money and not letting the taxpayers actually read the studies. But if they put it in their press release, it would be in here.

For press releases about open access articles, we always go out of our way to include a citation and link. That said, this took under a minute to find it using Google:

Yep, it is rare that something definitive appears without having an interim result published earlier, like on that link from last year. And after a year anything funded by the NIH will be in PubMed. I didn't see anything terribly wrong with this release but it may be a language/style issue, since it was written by the group in Spain and English may not be their first language.